Atherosclerosis is the leading cause of death and morbidity in the Western World. Alterations in lipid and lipoprotein metabolism are clearly related to atherogenesis. In particular elevations of low density lipoproteins are associated with high risk for premature coronary artery disease. Consequently, bile acid sequestrant resins are the drugs of choice to lower plasma cholesterol as they specifically decrease the low density lipoproteins. In response to these agents, however, there is a transient or even permanent increase in very low density lipoproteins. Elevations of this lipoprotein may be atherogenic as well. Furthermore, increased turnover (flux through plasma) of the very low density lipoproteins may be atherogenic since the catabolic products, known as remnants, are known to be associated with accelerated atherosclerosis. We are testing the hypothesis that all subjects placed on a bile acid binding resin will have increased flux through plasma of very low density lipoproteins. This will be true even though plasma levels of very low density lipoproteins are unchanged. We are testing this hypothesis by studying very low density lipoprotein turnover before and after three to four months of bile sequestrant therapy. The tritiated-glycerol technique will be used to quantify triglyceride turnover. The results of these studies should enable us to design better therapies for treatment of hypercholesterolemia.